Abstract

Therapeutic hypothermia has become the standard of care for newborns with perinatal asphyxia, for long term neuroprotection. Though, definitive literature on role of therapeutic hypothermia in out of hospital cardiac arrests in pediatric population is limited. Furthermore, little is known about the role of therapeutic hypothermia in cases of sudden unexpected postnatal cardiac arrest and asphyxia. We report a case of a Preterm infant born at 35 weeks, with cardiac arrest soon after birth that was treated successfully with therapeutic hypothermia for 72 hours.

Keywords

Introduction

Therapeutic hypothermia has become the standard of
care for newborns with perinatal asphyxia, for long term
neuroprotection. Hypothermia has been a tried and tested
strategy in neuroprotection in cardiopulmonary bypass surgeries
in both adult and pediatric population. With trials incorporating
therapeutic hypothermia in adults with out of hospital
cardiac arrests [1], showing improved neurologic outcomes,
international guidelines are strongly recommending use of the
same in the comatose adults. Conclusive evidence on the role
of therapeutic hypothermia in out of hospital cardiac arrests in
pediatric population, though, is limited, but many observational
studies have emphasised its growing relevance on the same [2].
Anecdotal reports too suggest that therapeutic hypothermia was
a standard of care for drowning, and even Reye’s syndrome prior
to the turn of this century.

Little is known about the role of therapeutic hypothermia in cases
of sudden unexpected postnatal cardiac arrest and asphyxia.
Given the vulnerability of the infant brain to the excitotoxicity,
therapeutic hypothermia may help attenuate the impact [2,3].
We report case of cardiac arrest soon after birth that was treated
successfully with therapeutic hypothermia for 72 hours.

Case Presentation

A late preterm (35 + 5 weeks’ gestation) male was found apneic,
unresponsive with asystole at 10 minutes of age while cared skin
to skin by the mother. The baby was born by Caesarean section
at 35 + 5 weeks due to preterm labour and previous caesarean
section with failure to progress. The mother was otherwise a
healthy 36-year-old with unremarkable antenatal course, no
history of recreational drugs, smoking or alcohol. Apgar scores
were 4 and 8 at 1 and 5 minutes, respectively, with favorable
cord gases (pH: 7.24, BE: -4). Baby required only brief positive
pressure ventilation for the first minute of age, with subsequent
successful transition to room air, he continued to do well, and
skin to skin was initiated by 6 min of age.

The baby was found apneic, bradycardic at 10 minutes of age,
cardiopulmonary resuscitation was immediately initiated,
including Intermittent positive pressure ventilation (IPPV)
followed by intubation after 5 minutes in view of no spontaneous respiratory efforts. Chest compression was also undertaken
after failure to establish circulation by 2 minutes of effective
IPPV, eventually escalating to epinephrine (2 intravascular
doses). Fluid resuscitation through emergent umbilical
venous catheter was accomplished, and finally, Naloxone was
administered, for possible maternal intrapartum morphine
induced cardiorespiratory compromise. Chest compression was
continued for 20 minutes for subsequent asystole. Baby was
finally, stabilized by 45 minutes of age, with heart rate above
100. Investigations post stabilisation revealed severe metabolic
acidosis (base excess of -23, with serum lactate of 11.8), but
no hypoglycemia. Further investigations suggested severely
deranged liver function, creatinine, and lactic acidosis. Troponin
levels were also markedly elevated Laboratory investigations
(Table 1). Patient was then transferred to level 3 neonatal
intensive care unit for further management.

On physical examination post resuscitation and stabilisation,
baby had decreased level of consciousness, no spontaneous
movements, hypotonic, depressed primitive and deep tendons
reflexes, consistent with moderate to severe encephalopathy
(Sarnat stage II-III). Therapeutic hypothermia was initiated after
discussion with parents, as there are no clear guidelines for
therapeutic hypothermia for babies with postnatal asphyxia.

Therapeutic hypothermia was continued for the next 72 hours
without side effects. He was mechanically ventilated for 6 days
and then successfully extubated to room air. During the initial
course of stabilization, hypotension and severe lactic acidosis was
managed by fluid resuscitation and inotropic support (Dopamine
and Dobutamine). Inotropes were weaned off by day 3 of life. He
was observed to be lethargic in the initial course, which gradually
improved over the next 48 hours.

Initial working diagnosis were sudden infant death syndrome (SIDS), with differentials being airway obstruction, sepsis and
inborn errors of metabolism. Detailed metabolic work up,
including but not limited to serum ammonia, plasma and urine
aminoacidogram, was undertaken in view of severe metabolic
acidosis, all of which were normal. The metabolic acidosis and
hyperlactatemia resolved in the next few days with adequate
fluids and inotropic support. An electrocardiogram, to rule out
long QT syndrome and an echocardiogram were performed, both
of which were normal.

The patient’s neurological condition showed progressive
improvement in the next few days. By 5 days of life, he was
alert, active with appropriate reflexes. Feed was initiated soon
after extubation, and achieved full oral feeds by the end of the
second week of life. An electroencephalogram and a Magnetic
resonance imaging of brain were completed on day 3 and day 5,
respectively, both of which were normal (Figures 1 and 2).

Figure 1: Full montage EEG on day 3 of life for our patient with normal finding.

Figure 2: MRI of the brain done on day 5 of life with normal finding.

Given the above clinical scenario with the supportive investigation
profile, the diagnosis was narrowed to possible Sudden Infant Death syndrome after excluding other differential diagnoses. He
was discharged home around 18 days of life. Home monitoring
was started for the next few months as per parental request, and
subsequently discontinued at 6 months of age. The infant was
followed closely at regular intervals at the Neonatal Follow up
clinic and pediatrician for the neurodevelopment assessment. At
36 months of age, he was doing well, in preschool and achieved
all his neurodevelopmental milestones appropriately.

Discussion

Sudden infant death syndrome (SIDS) remains the highest
cause of death in neonates and infants. 5% of the unexpected
deaths occur in the first postnatal week [4]. Sudden unexpected
postnatal collapse is a subset of catastrophic events occurring
within the first 24 hours of age. Though, sudden unexpected
postnatal collapse is rare but can lead to devastating outcomes,
in addition to, severe disability. These events have been found to
occur with skin to skin and prone positions in more than threequarters
of the time [4-7].

The ultimate goal of resuscitation, across ages, is to preserve
brain function. To this effect, therapeutic hypothermia has
increasingly become the standard of care to prevent acute brain
injury across all age groups and in diseases like traumatic brain
injury, stroke, and near drowning. In fact, it has been found to
be one of the most effective intervention to reduce neurologic
injury and morbidity post cardiac arrest in adult population
[8,9]. Mild hypothermia has also been found to be effective in
aborting seizures in cases of refractory status epilepticus in adults [10,11]. Therapeutic hypothermia has also, in the last few
decades, consolidated its role in the management of post cardiac
arrest and resuscitation of cold-water drowning of pediatric
population [12]. Its role in perinatal asphyxia has revolutionised
the management and outcomes in newborns. However little
evidence is available about the effect therapeutic hypothermia
may have on postnatal cardiac arrest after successful transition.

Injury secondary to encephalopathy post cardiac arrest in an
otherwise healthy newborn, is not a single event occurring at
the time of compromise, instead, it is an evolving process, just
like others. It undergoes the ischemia- reperfusion phases,
like the insult in a perinatal asphyxia, leading to energy failure,
accumulation of excitatory neuro-transmitters, loss of membrane
potentials leading to cytotoxic oedema, and then subsequent deterioration secondary to free radical formation, induction of
apoptosis and inflammatory cytokines. This secondary phase of
injury occurs in the ensuing hours and persists for days, often as a
result of, widespread apoptosis in the neuronal cells. Therapeutic
hypothermia, if initiated, before the onset of this secondary
phase of injury, reduces the apoptotic cell death [13,14].

Modest amount of hypothermia can generate a neuroprotective
effect [15]. Several multicenter trials have proven benefits of
therapeutic hypothermia in hypoxic ischemic encephalopathy in
term neonates [16]. Mechanisms of therapeutic hypothermia are
manifold. It reduces the cerebral metabolism, the accumulation
of excito-toxic neurotransmitters and the generation of oxygen
free radicals and inflammatory cytokines. Cerebral energy
phosphates are preserved and cerebral alkalosis and lactate are
reduced [17]. It also leads to the suppression of the apoptotic
mechanisms at play, and inhibits the activation of the microglia.

Hence, it wouldn’t be an exaggeration to say, therapeutic
hypothermia holds promise in the neuroprotective therapy in the
likelihood of such events.

The above mechanisms can, similarly, help play a role in the postresuscitative
management in babies with sudden unexpected
postnatal collapse or SIDS. As with HIE (hypoxic-ischemic
encephalopathy), therapeutic hypothermia, if initiated within
the first few hours of the event, can help improve neurologic
outcomes, as in our patient.

Conclusion

To our knowledge, this is the first case report of a late preterm
neonate associated with moderate encephalopathy secondary
to postnatal cardiac arrest successfully treated with therapeutic
hypothermia and had normal long neurodevelopment outcome.